Non-CPAP therapies in obstructive sleep apnoea - Dental ...

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Eur Respir J 2011; 37: 1000–1028
DOI: 10.1183/09031936.00099710
CopyrightßERS 2011

ERS TASK FORCE REPORT

Non-CPAP therapies in obstructive sleep
apnoea
W.J. Randerath*, J. Verbraecken*, S. Andreas, G. Bettega, A. Boudewyns,
E. Hamans, F. Jalbert, J.R. Paoli, B. Sanner, I. Smith, B.A. Stuck, L. Lacassagne,
M. Marklund, J.T. Maurer, J.L. Pepin, A. Valipour, T. Verse and I. Fietze,
the European Respiratory Society task force on non-CPAP therapies in
sleep apnoea

ABSTRACT: In view of the high prevalence and the relevant impairment of patients with                                   AFFILIATIONS
                                                                                                                        For the authors’ affiliation details,
obstructive sleep apnoea syndrome (OSAS) lots of methods are offered which promise definitive
                                                                                                                        please refer to the
cures for or relevant improvement of OSAS.                                                                              Acknowledgements section.
   This report summarises the efficacy of alternative treatment options in OSAS.                                        *W.J. Randerath and J. Verbraecken
   An interdisciplinary European Respiratory Society task force evaluated the scientific literature                     contributed equally to this work.
according to the standards of evidence-based medicine.
                                                                                                                        CORRESPONDENCE
   Evidence supports the use of mandibular advancement devices in mild to moderate OSAS.                                W.J. Randerath
Maxillomandibular osteotomy seems to be as efficient as continuous positive airway pressure                             Institute for Pneumology at the
(CPAP) in patients who refuse conservative treatment. Distraction osteogenesis is usefully applied                      University Witten/Herdecke,
in congenital micrognathia or midface hypoplasia. There is a trend towards improvment after weight                      Clinic for Pneumology and
                                                                                                                        Allergology, Centre of Sleep
reduction. Positional therapy is clearly inferior to CPAP and long-term compliance is poor. Drugs,                      Medicine and Respiratory Care,
nasal dilators and apnoea triggered muscle stimulation cannot be recommended as effective                               Bethanien Hospital
treatments of OSAS at the moment. Nasal surgery, radiofrequency tonsil reduction, tongue base                           Aufderhöherstraße 169–175
                                                                                                                        42699 Solingen
surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus
                                                                                                                        Germany
advancement cannot be recommended as single interventions. Uvulopalatopharyngoplasty, pillar                            E-mail: randerath@klinik-
implants and hyoid suspension should only be considered in selected patients and potential                              bethanien.de
benefits should be weighed against the risk of long-term side-effects. Multilevel surgery is only a
salvage procedure for OSA patients.                                                                                     Received:
                                                                                                                        June 29 2010
                                                                                                                        Accepted after revision:
KEYWORDS: Mandibular advancement devices, maxillomandibular osteotomy, multilevel surgery,                              Dec 25 2010
neuromuscular stimulation, uvulopalatopharyngoplasty, weight reduction

        ince the first description of their application        However, despite the efficacy of CPAP, many

S       in the early 1980s by SULLIVAN et al. [1],
        continuous positive airway pressure (CPAP)
and the more recent developments of automatic
                                                               patients suffer from local side-effects at the nose or
                                                               face, or discomfort due to the mask. Moreover,
                                                               CPAP does not allow for a permanent resolution of
positive airway pressure and bilevel therapy have              respiratory disturbances during sleep, but only
become the standard treatment of obstructive                   suppresses them while using the devices. There-
sleep apnoea syndrome (OSAS) [1]. Positive                     fore, many patients look for more comfortable or
airway pressure has proven to improve symp-                    curative treatment options. Both conservative and
toms, normalise the risk of traffic and workplace              surgical alternative therapeutic approaches have
accidents, and reduce the elevated sympathetic                 been described. However, there is a need to discuss
activity and risk for cardiovascular morbidities,              the scientific evidence for these therapies.
especially arterial hypertension. Most recently, it
has been shown that CPAP normalises mortality                  Thus, the European Respiratory Society funded a
in patients with severe OSAS [2, 3].                           task force with the aim of screening the scientific
                                                                                                                        European Respiratory Journal
                                                                                                                        Print ISSN 0903-1936
This article has online supplementary material available from www.erj.ersjournals.com                                   Online ISSN 1399-3003

1000                                   VOLUME 37 NUMBER 5                                                          EUROPEAN RESPIRATORY JOURNAL
W.J. RANDERATH ET AL.                                                                       ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS

literature on non-positive-pressure therapies, evaluating the                      4) Apnoea triggered muscle stimulation cannot be recom-
studies according to the criteria of the evidence-based                            mended as an effective treatment of OSAS at the moment
medicine, and giving recommendations for use in OSAS                               (negative recommendation C). Although tongue muscle train-
patients. The treatment of central sleep apnoea and periodic                       ing improves snoring, it is not efficacious in the treatment of
breathing was not in the focus of this work. The results of the                    sleep apnoea in general (negative recommendation B).
task force will be presented in this report and in more detail in
two following articles on conservative treatment options and                       5) Mandibular advancement devices (MADs) reduce sleep
two on surgical approaches.                                                        apnoeas and subjective daytime sleepiness, improve quality of
                                                                                   life compared with control treatments, and are recommended
                                                                                   in the treatment of patients with mild to moderate obstructive
METHODS
                                                                                   sleep apnoea (OSA) (A). There is emerging evidence on the
The members of the task force performed individualised                             beneficial cardiovascular effects of MADs. However, tongue-
literature searches for each topic area using electronic databases,                retaining devices (TRDs) cannot be recommended (C).
hand searches of relevant papers, and screening of reference
lists up to January 1, 2009. In addition, in May 2010 the authors                  6) Drug therapy is not recommended as treatment for OSA
screened the literature for more recent papers which might                         (most drugs C, for mirtazapine and protryptilline B).
change the conclusions and recommendations relevantly.
Reviews, guidelines and case reports were excluded. Studies                        7) Nasal dilators are not recommended for reducing snoring,
were included only if data of at least three subjects were                         or for improving sleep disordered breathing or sleep archi-
available and if sleep testing was performed using polygraphy                      tecture in OSA (D).
(cardiorespiratory monitoring) or polysomnography. Studies                         8) Nasal surgery as a single intervention cannot be recom-
were evaluated according to the Oxford Centre for Evidence-                        mended for treatment of OSA (negative recommendation C).
based Medicine’s levels of evidence (tables 1 and 2) [4]. The level
of recommendation (A, B, C or D) is given of the end of each                       9) Intranasal corticosteroids improve mild to moderate OSA in
section. All other tables are available in the online supplemen-                   children with co-existing rhinitis and/or upper airway
tary material (tables e1–e38).                                                     obstruction due to adenotonsillar hypertrophy (B). They may
                                                                                   also show some benefit with respect to both symptoms and
Changes reported are significant at the p,0.05 level, unless                       some sleep parameters. Intranasal corticosteroids can be
indicated otherwise. If required, statistical analysis was                         recommended as concomitant therapy in these situations.
performed to assess pre- versus postoperative differences in
outcome parameters using either Mann–Whitney U- or paired                          10) Tonsillectomy as a single therapy can be recommended for
t-test, as appropriate.                                                            treatment of OSA in the presence of tonsillar hypertrophy
                                                                                   in adults (C). Adenotonsillectomy can be recommended in
RECOMMENDATIONS OF THE TASK FORCE                                                  the presence of adenotonsillar hypertrophy associated with
1) There is a trend to worsening but not spontaneous cure of                       paediatric OSA (C). Radiofrequency tonsil reduction is not
sleep disordered breathing (C).                                                    recommended as a single procedure for the treatment of OSA
                                                                                   (negative recommendation D).
2) Weight reduction is associated with a trend to improvement
in breathing pattern, quality of sleep and daytime sleepiness,                     11) Uvulopalatopharyngoplasty (UPPP) is a single-level surgical
and is recommended to reduce this important risk factor (C).                       procedure effective only in selected patients with obstruction
                                                                                   limited to the oropharyngeal area. When proposing UPPP,
3) Positional therapy can yield moderate reductions in apnoea–                     potential benefits should be weighed against the risk of frequent
hypopnoea index (AHI) (younger patients, low AHI and less                          long-term side-effects, such as velopharyngeal insufficiency,
obese) but is clearly inferior to CPAP and, therefore, cannot be                   dry throat and abnormal swallowing. UPPP cannot be recom-
recommended except in carefully selected patients. Long-term                       mended except in carefully selected patients (C).
compliance with positional therapy is poor (C).
                                                                                   12) Laser assisted uvulopalatoplasty has not demonstrated any
                                                                                   significant effect, either on OSA severity or in symptoms or
 TABLE 1         Evidence levels                                                   quality of life domains, and is not recommended (negative
                                                                                   recommendation B).
 1a   Systematic analysis (systematic review) of RCTs with homogenous results
 1b   Particular RCT with limited dispersion                                       13) Due to insufficient evidence, radiofrequency surgery of the
 1c   Therapy, before its introduction all patients died                           soft palate may only be considered in patients with mild
 2a   Systematic review of cohort studies with homogenous results                  disease refusing or not requiring CPAP, as long as the
 2b   Particular cohort studies or RCT of lower quality
 2c   ‘‘Outcomes’’ research; ecological studies
 3a   Systematic review of case–control studies with homogenous results             TABLE 2        Grades of recommendation
 3b   Particular case–control study
                                                                                    A      Consistent level 1 studies
 4    Case studies and cohort studies or case–control studies of limited quality
                                                                                    B      Consistent level 2 or 3 studies or extrapolations of level 1 studies
 5    Expert opinions
                                                                                    C      Level 4 studies or extrapolations of level 2 or 3 studies

 RCT: randomised controlled trial.
                                                                                    D      Level 5 or inconsistent studies of other levels

                                                                                                                                                                         c
EUROPEAN RESPIRATORY JOURNAL                                                       VOLUME 37 NUMBER 5                                                             1001
ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS                                                                  W.J. RANDERATH ET AL.

individual anatomy appears suitable. It cannot be recom-             natural course OR prognosis OR evolution OR long-term
mended except in carefully selected patients (C).                    follow up. Of the selected papers, 24 studies reported data on
                                                                     the natural course of the disease.
14) Uvulopalatal flap as a single intervention can only be
recommended in selected cases for treatment of OSA (C).
                                                                     Overview of the evidence
Studies investigating the uvulopalatal flap with tonsillectomy
for OSA show a significant improvement of the severity of            There is a lack of knowledge on the age of onset and the course
OSA and quality of life, and this combined intervention can be       of sleep apnoea. It is widely accepted that snoring typically
recommended in selected patients (B).                                begins between the ages of 30 and 40 yrs, and that the
                                                                     incidence of sleep apnoea increases between ages 40 and
15) Pillar1 implants may be considered in patients with mild to      65 yrs. These data, however, do not reveal the progression of
moderate OSA, who are suitable with regard to their overall          the disorder with respect to its extent: neither concerning the
physical condition (not or only moderately obese, no or small        AHI, nor clinical symptoms, nor comorbidity.
tonsils and no sign of retrolingual obstruction), if conservative
approaches are not accepted by the patient. Pillar implants          Only a small number of studies [3, 5–11] have investigated the
cannot be recommended except in carefully selected patients (B).     natural course of sleep apnoea with respect to cardiovascular
                                                                     risk and mortality. The studies cited here monitored those
16) Due to insufficient evidence, radiofrequency surgery of the      patients who refused to undergo appropriate therapy. A small
tongue base as an isolated or combined procedure cannot be           number of studies has been performed investigating the course
recommended and may only be considered in selected patients          of the disease in patients with low AHI. No long-term follow-
intolerant to conservative treatment as long as the overall          up studies have been performed on sleepiness, the primary
condition appears suitable (non- or only moderately obese            symptom of OSA.
patients with retrolingual obstruction) (C).
                                                                     The present state of knowledge on this matter considering only
17) Due to insufficient evidence, hyoid suspension cannot be
                                                                     those follow-up studies with more than 20 participants can be
recommended and may only be considered in carefully
                                                                     summarised as follows: TISHLER et al. [12] studied healthy
selected patients (C) and may be combined with other
                                                                     persons (i.e. AHI ,5) and found a 5-yr incidence of 7.5% for
procedures in multilevel surgery (MLS) (B).
                                                                     OSA with an AHI .15, and of ,16% with AHI .10. The
18) Procedures such as laser midline glossectomy and tongue          incidence of sleep apnoea was independent of age, sex, BMI,
suspension (Repose1) have a small role as a single treatment         waist/hip ratio and serum cholesterol level. Interestingly, the
option for obese patients with moderate to severe OSA and            influence of BMI diminished with increasing age. The
cannot be recommended. There are at present no data about their      Wisconsin Sleep Cohort Study and the Cleveland Family
role in patients with mild disease (negative recommendation C).      Study revealed a significant increase over the time in AHI,
                                                                     especially among male, obese, older and snoring patients [13,
19) Genioglossus advancement cannot be recommended as a
                                                                     14]. Studies in the elderly revealed a progression of OSA in
single procedure for the surgical treatment of OSA (C).
                                                                     correlation with age over the long term, but not with BMI [15].
20) Maxillomandibular advancement (MMA) seems to be as               The Sleep Heart Health Study found that the increase of the
efficient as CPAP in patients with OSA who refuse conserva-          AHI upon an increase of the BMI over a 5-yr period was
tive treatment, particularly in a young OSA population               greater than a reduction of AHI under weight loss. The
without excessive body mass index (BMI) or other comorbid-           influence of body weight was significantly greater among
ities, and is recommended in this circumstance (B).                  males than among females [16]. In addition, PEPPARD et al. [17]
                                                                     reported a six-fold increase in odds ratio for the development
21) Distraction osteogenesis (DOG) can be recommended in
                                                                     of OSA, as accompanied by a 10% increase in body weight
congenital micrognathia or midface hypoplasia (mandibular
                                                                     within 4 yrs.
lengthening: B; midface advancement: C).
                                                                     There are conflicting results on the modulation of the severity
22) MLS cannot be recommended as a substitute for CPAP but
as a salvage procedure for OSA patients in whom CPAP and             of OSAS over time. While several investigators showed an
other conservative therapies have failed. Surgical success of        increase of severity in mild to moderate sleep apnoea patients
MLS for OSA is often unpredictable and less effective than           over time independently of the BMI, others failed to de-
CPAP (C).                                                            monstrate deterioration of upper airway resistance syn-
                                                                     dromes or found improvements of respiratory disturbances
CONSERVATIVE NON-CPAP TREATMENT OPTIONS                              [5, 18–24].
The natural course of OSA
Rationale                                                            Conclusions and recommendations
In the face of the high prevalence and the socioeconomic             There is a lack of population-based studies on the spontaneous
burden of OSAS the question arises if all patients have to be        course of OSA. However, both increasing incidence and
treated immediately after diagnosis or if spontaneous normal-        progression of AHI have been demonstrated for patients with
isation might be expected at least in a portion of patients.         mild to moderate OSA between the ages of 40 and 60 yrs, even
                                                                     independently of possible change in BMI. In contrast, a similar
Search strategy                                                      evolution has not been proven among the elderly and among
Databases individually searched: PubMed and Medline.                 those patients with higher initial AHI. In all age groups,
Keyword combinations: sleep apnoea AND progression OR                however, the primary risk factor for progression and elevated

1002                                            VOLUME 37 NUMBER 5                                     EUROPEAN RESPIRATORY JOURNAL
W.J. RANDERATH ET AL.                                                        ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS

incidence is the increase of body weight. An additional factor is   IBW (17–73%). The AHI decreased by 44¡22 h-1 (77%) (table
evidently male sex.                                                 e3) [29–31]. 94 patients (34.2%) showed a partial improvement
                                                                    in AHI, while 177 patients (64.4%) were cured of OSA. In the
At least in mild sleep-related breathing disorders future           pharmaceutical intervention studies, change in BMI was
research should address the influence of concomitant diseases       between 1.8 and 2.6 kg?m-2, accompanied by a decrease of
and their therapy on the course of sleep apnoea, the                the AHI between 2.8 and 16.3 h-1 (7–35.6%) (table e4) [32–34].
significance of snoring with respect to the development from
snoring to sleep apnoea, development of cardiovascular risks        An increase in deep sleep could be observed from +4 to +17%,
in snorers and sleep apnoea (table e1).                             while other studies found no change in deep sleep, or even a
                                                                    small decrease [35]. In all but one study, rapid eye movement
The presented data show a trend to worsening of sleep               (REM) sleep increased by 1–10%. An improvement of sleepi-
disordered breathing over time. Most studies are retrospective      ness based on self-assessment scales was reported after diet
and observational (case series). Based on these data, we state      and behavioural management, and after surgery, and after
that a spontaneous improvement cannot be expected (C).              pharmaceutical weight reduction [31–41]. In one study an
                                                                    unchanged mean multiple sleep latency test (MSLT) was
Weight reduction                                                    reported [41]. The evaluated study period was not always
Rationale                                                           indicated; the longest study period was 7 yrs [40].
Obstructive sleep-related breathing disorders are caused by
pharyngeal and/or laryngeal collapse. Pharyngeal fat deposits       Conclusions and recommendations
lead to a decrease in pharyngeal patency and underline the risk     Presented data show, under a weight reduction (BMI 0.2–
factor of obesity [25, 26]. Weight reduction will lead to a         24.4 kg?m-2), a trend to improvement in breathing pattern, an
decrease in critical closing pressure (Pcrit), and consequently     increase in REM sleep (1–10%) and deep sleep (0 to +17%), and
decreases the severity of OSA [27].                                 a decrease in daytime sleepiness. Most studies are retro-
                                                                    spective and observational (case series), and while randomised
Search criteria                                                     controlled trials have been published in recent years, they
Databases individually searched: PubMed and Medline.                report inconsistent results and, therefore, none provide high-
Keyword combinations: sleep apnoea syndromes AND weight             level evidence. Weight reduction is recommended to reduce
reduction. Of the 47 selected papers, three studies reported        the important underlying risk factor of obesity. Most available
data on the mechanisms of action of weight reduction (change        studies have level 4 (C).
in Pcrit, change in pharyngeal cross-sectional area, change in
respiratory mechanics).                                             Positional therapy
                                                                    Rationale
Overview of the evidence
                                                                    The number and duration of respiratory disturbances depend
51 studies were identified, reporting on the effect of weight
                                                                    on body position and sleep stage [42–46]. The cross-section and
reduction in adults, 25 on diet instructions, 24 on surgical
                                                                    the closing pressures of the pharynx differ according to body
intervention (one study evaluated both) and three on pharma-
                                                                    position and stage of sleep [47–49]. Ventilatory drive is
ceutical weight reduction. One study performed in extremely
                                                                    dependent on body position. Thus, there is ample evidence
overweight adolescents was also included [28]. Six studies
                                                                    suggesting a positive effect of a lateral position during sleep.
were published by the same study group. 17 studies on diet
                                                                    Using the definition of positional OSA as a supine AHI of at
instruction intervention were case series, or evidence level 4.
                                                                    least twice that in the lateral position, a prevalence of ,50% is
Surgical treatment (gastric banding, gastroplasty or gastric
                                                                    reported [50].
bypass) was evaluated in 24 studies, which were also all case
series. Pharmaceutical weight reduction was reported in two
                                                                    Search criteria
case series in the same population and in one randomised
                                                                    Databases individually searched: PubMed and Medline.
controlled trial. Only studies with sibutramine were per-
                                                                    Keyword combinations: sleep apnoea AND positional therapy.
formed. 10 studies were based on polygraphy (seven diet
                                                                    A recent review on medical therapy of OSA was screened. 27
studies, three surgery studies, one both). Seven of these
                                                                    of the 39 articles found were excluded, mostly because they did
polygraphic studies were performed in Finland. Weight
                                                                    not contain data on the efficacy of positional therapy in the
changes have been calculated partly as change in kg, partly
                                                                    treatment of OSA (table e5).
as change in BMI, partly as change in excess body weight
(EBW) (and expressed as percentage EBW) or as change in
                                                                    Overview of the evidence
percentage of ideal body weight (IBW). Therefore, an overall
change in body weight related to change in AHI cannot be            Clinical experience and observational studies suggest that the
expressed (tables e2 and e3).                                       patients exhibiting a large decrease in AHI in the lateral
                                                                    position compared with the supine position tend to have a
In the diet intervention studies, mean BMI reduction of             lower AHI, to be younger and to be less obese [44, 51].
4.7¡2.5 kg?m-2 was accompanied by a decrease of the AHI             Accordingly, patients with a clear improvement of the AHI
by 21¡13 h-1 (44%) (table e2). 246 patients (39%) showed a          with positional therapy tended to be younger, to have a lower
partial improvement in AHI, while 145 patients (23%) were           AHI and to be less obese [42, 52, 53]. It is not possible to extract
cured of OSA. In the surgery intervention studies, change in        from the data whether AHI, age or obesity is the best predictor
BMI was between 10–24.4 kg?m-2. Three studies reported
reduction of the percentage of IBW between 26.4 and 82%
                                                                    of treatment success. It is more likely that these parameters are
                                                                    mutually interrelated.                                                 c
EUROPEAN RESPIRATORY JOURNAL                                        VOLUME 37 NUMBER 5                                            1003
ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS                                                                     W.J. RANDERATH ET AL.

Different devices such as tennis balls, vests, positional alarms,     [66, 69, 71–77] or between appliance designs [78–87]. Two
verbal instruction and pillows are used to avoid the supine           studies reported long-term results after 2 and 4 yrs of
position [53–58]. There are no data comparing the different           treatment, respectively [86, 88]. The sample sizes in these
devices, with the exception that verbal instructions seem to be       studies ranged from 19 to 114 patients. The patients were
less effective than a positional alarm [42, 59].                      overweight or obese (mean BMI 26–33 kg?m-2).
A number of short-term studies demonstrate significant but            MADs have been shown to widen primarily the lateral parts of
moderate effects on AHI. However, most studies were                   the upper airway [89] and to reduce pharyngeal collapsibility
uncontrolled and small [52–54, 56, 57, 60]. More importantly,         [90]. MAD treatment reduced sleep apnoeas compared with
even in a subset of patients with clear positional sleep apnoea,      placebo in all studies [62–66, 68–70]. Treatment success with
effectiveness was limited. Two uncontrolled studies suggested         MAD, defined as an AHI of ,5, was found in 19–75% of the
some improvement of sleep stages or daytime symptoms with             patients and an index of ,10 was reported in 30–94% of the
positional therapy [57, 58].                                          patients [63–68, 70–79, 81, 82, 84, 85, 87, 91, 92]. Sleep apnoeas
                                                                      increased slightly and some patients discontinued treatment
One study had a clinically meaningful follow-up period of             in the longer term [86, 88]. Milder sleep apnoea, supine-
2 yrs [56]. Only 29% used the positional vest in this study after     dependent sleep apnoeas, female sex and less obesity have
2 yrs [56]. In a randomised crossover comparison with CPAP,           been related to treatment success with MADs [63, 65, 70, 76, 82,
positional therapy (elevation of head and shoulder) was clearly       92, 93]. CPAP reduced sleep apnoeas more efficiently or gave a
inferior in terms of the AHI [61].                                    higher success rate in all studies [66, 69, 71–77].

Conclusions and recommendations                                       Subjective daytime sleepiness decreased from MAD treatment
Patients with a clear improvement of the AHI with positional          compared with placebo according to many short-term studies
therapy tend to be younger, to have a lower AHI, and to be less       [62, 64, 66, 68, 70], although control treatment may also give
obese. Positional therapy can yield moderate reductions in AHI        positive effects [64, 69]. The effect on sleepiness was usually
but is clearly inferior to CPAP. Long-term compliance with            similar between CPAP and MADs [66, 72, 74–77], but CPAP
positional therapy is poor. If positional therapy is used, sleep      may produce a better outcome than MAD [69, 71, 73]. Snoring
studies are recommended to document individual success.               is more effectively controlled with CPAP than with MADs [72],
Long-term compliance has to be secured by follow-up studies.          but there is a better effect from MADs than placebo [63, 64].
                                                                      Persistent snoring during MAD treatment may be a sign of a
Recommendation: positional therapy is not recommended for             poor apnoea control [71]. Promising effects on blood pressure,
the treatment of OSA, except in carefully selected patients. If       cardiac function, endothelial function, markers of oxidative
positional therapy is used, sleep studies have to be performed        stress and simulated driving performance have been reported
to document individual success. Long-term compliance has to           from MADs [66, 69, 84, 94–99].
be secured by follow-up studies (C).
                                                                      Titratable custom-made MADs have been used in the
Intraoral protrusion devices                                          majority of the efficacy studies. Comparison between device
                                                                      designs indicated that there are only minor differences in
Mandibular advancement devices
                                                                      treatment effects between custom-made devices [78, 80, 83,
Rationale
                                                                      84], while a prefabricated device was less effective [85]. The
MADs reposition the lower jaw forwards and downwards
                                                                      degree of mandibular advancement is crucial, since a non-
during sleep. The treatment aims to widen the upper airways
                                                                      advanced device is ineffective on sleep apnoeas [62, 65, 70]
in order to improve the upper airway patency, and reduce
                                                                      and may even increase the apnoea frequency [62]. A titration
snoring and obstructive sleep apnoeas.
                                                                      procedure is therefore recommended to achieve optimal
                                                                      results [87, 91, 100, 101].
Search strategy
Databases individually searched: PubMed and Medline.                  Initial side-effects, such as jaw discomfort, tooth tenderness,
Keyword combinations: sleep apnoea syndromes AND ortho-               excessive salivation and/or temporary occlusal changes, were
dontic appliances; functional or removable, activator appli-          reported in slightly more than half of the patients [63, 65, 69,
ances or mandibular advancement, sleep apnoea AND oral                71–74, 78], and more frequently from MAD than from a control
appliances, mandibular advancement devices, mandibular                plate [64]. After 1 yr, 76% of the patients continued treatment
repositioning appliances, mandibular advancement splints or           [92] and 65% were still using their devices after 4 yrs [88].
mandibular repositioning splints were individually used. Out          Compliance monitors have been introduced [102]. Compliance
of 79 articles in total, 29 were excluded because the topic was       with MADs has been reported to be higher than with CPAP
covered in the randomised controlled trials or the aims were          [66, 77] and MADs are often preferred by the patients [71, 72,
not directly related to the efficacy of the device. 27 randomised     74, 75, 77].
controlled trials about treatment effects from MADs and five
randomised controlled trials in particular topics were found          Conclusions and recommendations
(table e6). In addition, 18 other clinical trials that highlighted    MADs are recommended for the treatment of patients with
particular aspects of MAD treatment were identified.                  mild to moderate OSA (A) and in patients who do not tolerate
                                                                      CPAP. MADs reduce sleep apnoeas and subjective daytime
Overview of the evidence                                              sleepiness and improve quality of life compared with control
The 27 randomised controlled trials evaluated the effects             treatments. There is emerging evidence on beneficial cardio-
of MADs compared with placebo treatment [62–70], CPAP                 vascular effects from MADs. CPAP more effectively reduces

1004                                             VOLUME 37 NUMBER 5                                       EUROPEAN RESPIRATORY JOURNAL
W.J. RANDERATH ET AL.                                                        ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS

sleep apnoeas, while the positive effects on symptoms and           [108]. In healthy subjects, these muscles stabilise the phar-
health are more similar between these treatments. Patients          yngeal airway. In order to counterbalance the collapsible
generally prefer MADs over CPAP. The device should be               forces, the upper airway muscles have to contract more
custom-made, evaluated and advance the mandible at least            intensively [109]. The genioglossus muscle is one of the most
50% of maximum protrusion. A titration procedure is essential.      important dilators. It pushes forward the tongue and enlarges
Re-evaluation with a new sleep apnoea recording is necessary,       the cross-sectional area of the upper airways. Its activity is
since the improvement of OSA symptoms is an imprecise               increased in OSAS during wakefulness, which has been
indicator of treatment success. This is particularly important in   proposed to be a compensatory mechanism [110, 111]. Based
patients with a more severe disease and in patients with            on these findings the question arose of whether direct or
concomitant health problems. Follow-up should be performed          indirect stimulation of the upper airway muscles optimise the
regularly over the long term.                                       dilating forces and increases the width of the upper airways.
                                                                    Present developments focus mainly on hypoglossus nerve
Tongue retaining devices                                            stimulation. Electrical stimulation is performed during sleep to
Rationale                                                           counteract respiratory disturbances whenever they appear.
TRDs are designed to produce a suction of the tongue into an        Conversely, training procedures have been developed aiming
anterior bulb, move the tongue forwards and widen the upper         at improving the altered upper airway muscles. These training
airway dimensions during sleep, in order to reduce obstructive      procedures are performed during wakefulness.
sleep apnoeas and snoring.
                                                                    Search criteria
Search strategy                                                     Databases individually searched: PubMed. Keyword combina-
Databases individually searched: PubMed and Medline.                tions: neurostimulation OR electrical stimulation OR upper
Keyword combinations: sleep apnoea AND tongue retaining             airway muscles OR genioglossus stimulation OR hypoglossus
device or tongue stabilizing device were individually used for      nerve stimulation AND sleep apnoea syndrome. 28 studies
searches in PubMed. In total, three randomised controlled           were found, of which 13 were included in the further
trials [59, 103, 104] and three other trials with small sample      evaluation. The other studies did not focus on the electrical
sizes were found (table e7) [105–107].                              stimulation of the upper airway muscles, but on physiological
                                                                    or pathophysiological aspects, effects of MADs or drugs on the
Overview of the evidence                                            upper airway muscles or surgical or anaesthesiological aspects
The three randomised controlled trials [59, 103, 104] evaluated     (table e8).
the effects of TRDs on sleep apnoeas and symptoms and
analysed predictors (table e7). One randomised controlled trial     Overview of the evidence
showed significant effects from TRD on sleep apnoeas com-           Acute efficacy of electrical stimulation on upper airway patency
pared with a control device in patients with mild to moderate       Stimulation of the upper airway muscles with surface and
sleep apnoea [103]. A comparison between a tongue stabilising       intraneural electrodes has proven to reduce the resistance of
device and MAD in another randomised controlled trial showed        the upper airways both in healthy persons and patients with
a similar apnoea reduction from the two devices, although the       OSAS [27, 112–118]. The stimulation of the genioglossus
patients preferred MADs [104]. TRD was compared with                muscle most effectively reduces resistance and the critical
posture alarm and positional treatment in 60 patients with          pressure Pcrit [113, 115, 116].
positional dependency and moderate OSA. TRD reduced sleep
apnoeas in the supine position and gave some benefit for            Efficacy of apnoea triggered neurostimulation in clinical use
patients who continued to sleep in that position [59]. One of the   There are conflicting results on the clinical efficacy of apnoea
clinical trials showed an effect of TRD on oxygen desaturations     triggered neurostimulation. Intraneural stimulation of the
[106], while the other two studies did not show any reduction in    hypoglossus nerve and transcutaneous electrical stimulation
sleep apnoeas from this type of treatment in small samples of       of the genioglossus muscle showed significant improvements
moderate to severe sleep apnoea patients [105, 107].                of respiratory disturbances and sleep parameters without
                                                                    adverse effects [112, 119]. In contrast, other groups failed to
Conclusions and recommendations                                     find an enlargement of the upper airways by transcutaneous or
TRDs are not recommended for patients with OSA. They can            intramuscular stimulation during wakefulness or sleep.
be used in selected patients with mild to moderate OSA (C),         However, undesirable contractions of the platysma or tongue
when other treatments have failed or are not possible. These        were observed and arousals were induced [114, 116, 120, 121].
patients may have a trial with this device, provided that the       OLIVEN and co-workers [115, 116] studied the critical phar-
treatment effect is monitored and the patients are strictly         yngeal pressure under intraneural hypoglossus and intramus-
followed up. A few studies show reductions in sleep apnoeas         cular and surface genioglossus stimulation and demonstrated
from TRDs, although symptomatic effects are mainly unknown          that the patency of the upper airways depends more on the
and compliance might be a limitation.                               effective stimulation of the genioglossus muscles.

Training of the upper airway muscles and hypoglossus                Tongue muscle training by electrical stimulation
nerve stimulation                                                   Electrical stimulation has proven to be effective in the
Rationale                                                           rehabilitation of skeletal muscles after injury. It activates motor
The obstruction of the upper airways is accompanied by
diminished neuromuscular activity of the dilating muscles
                                                                    units in healthy muscles, which cannot be reached voluntarily.
                                                                    Based on these findings the question arises if training of the        c
EUROPEAN RESPIRATORY JOURNAL                                        VOLUME 37 NUMBER 5                                           1005
ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS                                                                      W.J. RANDERATH ET AL.

pharyngeal muscles, especially the genioglossus muscle, during        Overview of the evidence
the daytime might improve the respiratory disturbances during         25 studies (24 papers) were identified, reporting the effects of
sleep. Preliminary results of case studies and one cohort showed      24 drugs and recruiting between them 413 subjects. Due to
improvements of the AHI, daytime sleepiness and snoring [122,         small size, a lack of detail in reporting the methods, in
123]. The only placebo-controlled double-blind study on tongue        particular randomisation, and incomplete data, few of the
muscle training found an improvement of snoring but no                studies scored higher than 2b for level of evidence. Three
significant reduction of AHI [124].                                   studies included protriptyline, their results were subjected to
                                                                      meta-analysis and scored as 1a (table e9) [127].
Oropharyngeal exercise
In addition to electrical stimulation of the upper airway             Protriptyline is a tricyclic antidepressant that inhibits re-uptake
muscles, the question of whether exercises may improve                of serotonin and noradrenaline. It might reduce the proportion
symptoms of OSAS has been studied. PUHAN et al. [125]                 of REM sleep in people with REM predominant OSA and
showed a reduction, but not normalisation, of the AHI after           increase the airway tone mediated by serotonin acting on the
didgeridoo playing. More recently, GUIMARAES et al. [126]             genioglossus via the hypoglossal nerve. However, there was no
randomised 31 patients with moderate OSAS to 3 months of              impact on respiratory indices but there was an improvement in
oropharyngeal exercises or sham therapy. They found sig-              daytime symptoms in two out of three trials, presumably due
nificant, but limited, reduction of the AHI. Moreover, snoring,       to a nonspecific alerting effect of the drug. Adverse side-
daytime sleepiness, neck circumference and self-assessment            effects, such as dry mouth and urinary symptoms, were
questionnaires demonstrated improvements. It is unclear               commonly reported. Protriptyline does not have any place in
which of the several exercises was most relevant for the              the routine treatment of OSA [128–130].
treatment effect.
                                                                      Specific serotonin re-uptake inhibitors such as paroxetine have
                                                                      been investigated as possible treatments for OSA. In a small
Conclusions and recommendations
                                                                      single night study, paroxetine 40 mg had no impact on AHI
Apnoea triggered muscle stimulation cannot be recommended             compared to placebo with severe OSA [131]. By contrast, in a
as an effective treatment of OSAS at the moment (C). Although         study with 6-week treatment arms paroxetine 20 mg was
oropharyngeal exercise has shown limited effects on snoring
                                                                      shown to reduce AHI to 23.3 compared with 30.3 for placebo.
and respiratory disturbances, its role is not clear at the moment
                                                                      There was a positive impact on respiratory events in non-REM
and, therefore, it cannot be recommended (B).
                                                                      sleep but no effect in REM sleep, and no improvement in
                                                                      daytime symptoms [132].
Drug therapy
Neuromediator modulators                                              Mirtazapine is another drug with antidepressant activity that
Rationale                                                             acts as an agonist at some serotonin receptors and can also
Although there may be a predisposing airway abnormality, it is        increase serotonin secretion. This might increase sertonergic
changes in respiratory drive, airway tone or surface forces that      tone to the hypoglossal nerve, which could be particularly
cause airway closure during sleep. Pharmaceutical agents might        helpful during REM sleep. Reductions in the AHI were
reduce sleep apnoea by increasing respiratory drive, changing         reported in one study [133] but could not be reproduced in
sleep structure (in particular suppressing REM sleep), increas-       two multicentre trials, while many participants reported side-
ing upper airway muscle tone, changing respiratory and car-           effects of sleepiness and weight gain [134]. The drug cannot be
diovascular reflexes that may perpetuate apnoeas and reducing         recommended for use in OSA.
surface forces that encourage closure of the upper airway.            Cholinergic agonists have been investigated as possible
                                                                      treatments for OSA. In a single night study 10 subjects had
Search strategy                                                       an AHI of 41 on physostigmine compared with 54 on placebo
Databases individually searched: PubMed and Medline. Key-             [135]. The greatest impact was on apnoeas during REM sleep
word combinations: Sleep apnoea/apnoea (drug* or pharma-              and there was an inverse relationship with BMI, such that
cological and (treatment*)) or progesterone or progestogen            slimmer subjects had a greater fall in AHI. The drug was given
or medroxy* or ‘‘tricyclic anti depressant*’’ or protriptyline or     intravenously, making it impractical for home use. There have
amitriptyline or imipramine or ssri or fluoxetine or clonidine        been no studies with oral cholinergic agents.
or modafinil or stimulant* or Buspirone or doxapram or
dopram or naloxone or narcan or ‘‘opiod antagonist*’’ or              Acetazolamide inhibits carbonic anhydrase, producing a
nicotin* or ‘‘ACE inhibitor*’’ or ACE-inhibitor* or cilazapril        metabolic acidosis that increases ventilatory drive. It was
or captopril or enalapril or fosinopril or imidapril or lisinopril    shown to reduce the AHI in a study of 10 subjects but there
or perindopril or quinapril or ramipril or trandolapril or ‘‘anti     was no positive impact on daytime symptoms after 1 week of
hypertensive*’’ or anti-hypertensive* or antihypertensive* or         treatment [130]. The subjects who had responded best to the
baclofen or mirtazapine or steroid* or *steroid or fluticasone.       drug were offered a more prolonged trial of treatment but only
                                                                      one could tolerate it in the long term. It has no role in the
Reports on snorers or subjects with predominantly central             routine management of OSA.
apnoeas were excluded. Even with these filters a large number
of low quality studies were identified. For nearly all of the         In a single night study with 10 subjects, phosphocholinamin
drugs that have been trialled in the past 20 yrs there is at least    was given as a topical nasal lubricant administered twice
one randomised controlled trial and so uncontrolled studies           overnight which resulted in an AHI of 14 compared with 24
and review articles were excluded.                                    with placebo [136]. In view of the duration of the study it is not

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W.J. RANDERATH ET AL.                                                          ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS

known whether this might improve daytime symptoms but the             steroids and sleep apnoea, sleep apnoea and fluticasone, sleep
drug was not recommended for long-term use due to anxiety             apnoea and triamcinolone, sleep apnoea and budesonide,
about aspiration causing lipoid pneumonia. There are no               OSAS and corticosteroids.
published studies of any other candidate substances.
                                                                      Overview of the evidence
Among the other drugs that have been trialled, naltrexone,            We identified only one single-centre study with a small sample
theophylline and aminophylline have been shown to reduce              size that investigated the effects of intranasal corticosteroid
the number of respiratory events overnight but this was at the        application for 4 weeks on polysomnographically diagnosed
expense of sleep continuity and total sleep time, which makes         sleep parameters in adult patients with moderate OSA and co-
them unsuitable agents for the treatment of OSA. Omeprazole           existing (perennial or seasonal) rhinitis [140]. There was a modest
has been said to reduce the frequency of attacks of apnoea in         but significant decrease in AHI and an improvement in nasal
subjects who had both OSA and gastro-oesophageal reflux               airflow resistance; however, there were no significant improve-
disease, but no sleep studies were performed on treatment and         ments in oxygenation indices, sleep quality or snoring noise.
the attacks may well have been episodes of laryngospasm due
to acid reflux, not episodes of OSA. Medroxyprogesterone,             Five studies with a total of 136 children (age range 1–14 yrs)
doxapram, clonidine, mibefradil, cilazapril, buspirone, ondan-        with mild to moderate OSA were identified. Two studies were
setron and sabeluzole have all been investigated and none has         conducted as open clinical trials without a control group, one
been shown to reduce the frequency of respiratory events in           study investigated the effects of budesonide and montelukast,
people with OSA or to improve daytime symptoms.                       using a case control design, and two studies were conducted as
                                                                      prospective, randomised, placebo-controlled trials. Most of the
Conclusions and recommendations                                       children included in these reports had evidence of co-existing
At the present time there is no evidence that any drug is likely      rhinitis with or without adenotonsillar hypertrophy. All
to benefit an unselected patient with OSA. Small studies have         included reports observed significant treatment-associated
reported positive effects of certain agents on short-term             improvements in the AHI (mean pre-treatment AHI range
outcomes. Longer studies with measures of symptomatic                 3.7–11 versus treatment-associated mean AHI range 0.3–6).
responses of cholinergic agents and upper airway lubricants           Three reports furthermore showed significant improvements
are supported by the results of single night studies already          in oxygenation indices and two studies demonstrated
published. It is likely that better characterisation of the           improved sleep quality. The data are, however, inconsistent
predominant mechanisms of OSA in individual patients will             with respect to sleep architecture and adenoidal size (table e10)
lead to better results and this also needs further study. Drug        [140–145].
therapy is not recommended as treatment for OSA (most drugs
                                                                      Conclusions and recommendations
C; for mirtazapine and protryptilline B).
                                                                      Intranasal steroids, as a single intervention, are not recom-
                                                                      mended for treatment of adult OSAS (C). Intranasal steroids
Nasal steroids
                                                                      are recommended for childhood OSAS in the presence of co-
Rationale
                                                                      existing rhinitis and/or upper airway obstruction due to
A particularly frequent cause of nasal obstruction is allergic        adenotonsillar hypertrophy (B).
rhinitis, either seasonal or perennial. There are a number of
reports suggesting worsening of subjective sleep quality and          Nasal dilators
quality of life measures in both adults and children with             Rationale
allergic and perennial rhinitis [137]. Vice versa, CANOVA et al.      The nasal vestibule is a major site of resistance to airflow in
[138] demonstrated an increased prevalence of perennial               healthy subjects. A high nasal resistance may increase snoring.
allergic rhinitis in patients with OSA (11%) compared to case         Activation of the alae nasi and alar retraction reduce resistance
controls (2.3%). In addition to the obstructing effects of allergic   to airflow and improve ventilation. Nasal dilators might
rhinitis, inflammation of the nasal mucosa may contribute to          improve sleep and breathing by widening the nostrils. They
the development of adenotonsillar hypertrophy, one of the             are fitted to exert a dilating force on the nasal valves by means
most frequently observed abnormalities in children with OSA.          of its elasticity.
Intranasal corticosteroids are commonly used to treat rhinitis.
A recent Cochrane review on intranasal corticosteroids showed         Search strategy
significant efficacy of intranasal corticosteroids in improving       Databases individually searched: PubMed and Medline.
nasal obstruction symptoms and in reducing adenoid size               Literature search using the terms obstructive sleep apnoea
[139]. Consequently, this may influence the anatomic compo-           AND nasal dilator (no limits) was performed. Original studies
nent by decreasing upper airway resistance at the nasal,              published in English before April 2010 were included. In
adenoidal, and/or tonsillar levels. Therefore, topical nasal          addition, the reference list of the included trials was evaluated.
steroids may influence sleep apnoea severity both in children         In total, 14 studies (two randomised controlled trials and 12
and adults.                                                           other clinical trials) could be identified, published between
                                                                      1988 and 2005.
Search criteria
Databases individually searched: PubMed and Medline.                  Overview of evidence
Keyword combinations: sleep apnoea and intranasal corticos-           Nasal dilation increases nasal cross section by 14–25% and is
teroids, sleep apnoea and inhaled corticosteroids, sleep apnoea
and intranasal steroids, sleep apnoea and corticosteroids, nasal
                                                                      associated with a distinctive and sustained reduction in nasal
                                                                      resistance and the oral fraction of ventilation during sleep          c
EUROPEAN RESPIRATORY JOURNAL                                          VOLUME 37 NUMBER 5                                           1007
ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS                                                                  W.J. RANDERATH ET AL.

[146]. External nasal dilators are well tolerated [147]. They       obstructive apnoeas and hypopnoeas during sleep associated
were able to reduce the maximum snoring intensity in one            with nasal occlusion under experimental nasal obstruction
study [148], but in another study snoring was not influenced at     [163–165]. Similarly, there is evidence of sleep-related breath-
all [149]. Sleep architecture remains almost unchanged in           ing disorders associated with nasal obstruction as a result of
patients with habitual snoring [147, 149] and is improved           bilateral nasal packing after nasal surgery [166–169]. One
slightly in patients with OSA [146]. OSA severity was reduced       potential limitation in these reports may be the potential
in one study with 10 patients with OSA and nasal obstruction        influence of general anaesthesia on the prevalence of post-
[146], but not in another study with 30 patients with OSA [150],    operative upper airway obstruction. In a recent report, how-
and in a study with 18 patients with upper airway resistance        ever, ARMENGOT et al. [170] demonstrated equivalent episodes
syndrome there was no additional effect on sleep disordered         of nocturnal hypoxaemia, both in patients who had nasal
breathing [151]. It is possible that there are parameters           packing postoperative nasal surgery and in those who had
predicting the efficacy of the devices, such as hyperplasia or      nasal packs for epistaxis but did not receive surgery.
hypertrophy of the lower turbinates, septal deviation, allergic
rhinitis, no or only minor pharyngeal obstruction, or age           In summary, there is evidence of a protective effect of nasal
,55 yrs (table e11) [152].                                          breathing on upper airway stability. The current literature
                                                                    furthermore suggests that patients with OSA are more likely to
Internal nasal dilation reduces nasal resistance by 31–65% [153,    breathe through the high resistance pathway of the mouth,
154] and thereby improves the airflow [45]. Devices have a          thereby promoting more negative intraluminal pressure in the
weak effect on snoring in patients without nasal pathology          pharynx, and predisposing to pharyngeal occlusion and, thus,
[155], even in populations with different external nose             OSA events. Moreover, there is evidence on both inducing
structures (Caucasians and Japanese) [156], but their use           and worsening of sleep disordered breathing due to nasal
resulted in a substantial decrease in snoring noise in patients     occlusion.
with habitual snoring and/or OSA [157]. The devices have
only little or no effect on the number of apnoeas, hypopnoeas       Effects of nasal surgery on OSA
and oxygen saturation during sleep, or hypersomnolence              Rationale
during the day (table e12) [154, 157, 158].                         Due to the impact of nasal obstruction, improved nasal patency
In summary, the published data do not support the hypothesis        is expected to alleviate sleep disordered breathing. Further-
that nasal dilators are effective in reducing snoring, or in        more, there is an expected relationship between nasal airway
improving sleep disordered breathing or sleep architecture in       obstruction and CPAP tolerance, providing a physiological
OSA. Nasal dilators are not recommended for reducing                basis for improved CPAP compliance after nasal surgery [171].
snoring, or for improving sleep disordered breathing or sleep       Accordingly, the aim of this review is to assess the efficacy of
architecture in OSA (D).                                            nasal surgery on sleep apnoea severity, sleep quality and
                                                                    symptoms in adults with diagnosed OSA.
SURGICAL THERAPY
                                                                    Search criteria
Pathophysiological impact of nasal obstruction in the
                                                                    The authors performed searches in Pubmed and Medline. In
development of OSA
                                                                    addition, the authors underwent a manual search of the
Breathing through the human nose appears to have an effect
                                                                    reference section of each cited article. Keyword combinations:
on both ventilation and upper airway muscle tone. In an
                                                                    OSA and nasal obstruction, OSA and nasal surgery, sleep
experimental study, MCNICHOLAS et al. [159] previously
                                                                    apnoea and nasal surgery, sleep apnoea and nasal obstruction,
demonstrated increased ventilation during nasal ventilation
                                                                    sleep apnoea and nose, nasal ventilation and OSA. Studies
compared with mouth breathing. WHITE et al. [160] investi-
                                                                    with snorers only or those with sleep breathing disorders other
gated the effects of local nasal anaesthesia on ventilation
                                                                    than OSA, and studies in which nasal surgery was associated
during sleep in healthy males. The application of lidocaine
                                                                    with other surgical procedures in the treated subject (i.e.
resulted in a four-fold increase in the number of both central
                                                                    adenotonsillectomy or others) were excluded.
and obstructive apnoeas, suggesting a stimulating effect of
nasal airflow on respiratory muscle activity and upper airway
                                                                    Overview of the evidence
stability. The latter has been confirmed by BASNER et al. [161],
                                                                    14 reports with adult patients suffering from mild to severe
who demonstrated that nasal ventilation was associated with
                                                                    sleep disordered breathing and nasal obstruction have been
higher upper airway dilator muscle activity than breathing
                                                                    published either as case series or retrospective analyses, and
through the mouth in healthy volunteers. More recently,
                                                                    one report [172] was conducted as a prospective, randomised,
KOUTSOURELAKIS et al. [162] investigated the relationship
                                                                    sham-controlled trial (table e13) [172–183]. The most frequently
between breathing route and apnoeic events in patients with
                                                                    observed pathologic finding in the preoperative ear, nose and
OSA and controls. Patients with OSA had more frequent oral
                                                                    throat examination was nasal obstruction due to deviated nasal
breathing epochs during sleep than controls. Oral breathing
                                                                    septum. Accordingly, septal surgery (submucosal resection
epochs furthermore correlated with respiratory disturbances
                                                                    with or without turbinectomy) was the most frequently
during sleep.
                                                                    applied surgical technique in these reports. All the studies
It may be argued that nasal obstruction may predispose to           (n55) that have performed rhinomanometry reported signifi-
sleep disordered breathing. In fact, a number of studies            cant postoperative improvements in total nasal resistance,
demonstrated an increased number of arousals, more frequent         indicating postoperative improvements in nasal airway
sleep stage changes, and/or an increase in the number of            patency in the patients.

1008                                           VOLUME 37 NUMBER 5                                      EUROPEAN RESPIRATORY JOURNAL
W.J. RANDERATH ET AL.                                                        ERS TASK FORCE: NON-CPAP THERAPIES FOR OSAS

Only two studies [180, 181] reported significant improve-           Overview of the evidence in children
ments with regard to respiratory disturbances. One study [177]      38 ‘‘particular case–control studies’’ (n510; evidence level 3b),
reported a significant improvement in AHI and sleep archi-          case–control studies of limited quality (n52; level 4), and case
tecture in those with normal preoperative cephalometric             series without controls (n526; level 4) investigating patients
measurements, but no beneficial effect in a group of patients       between 1 and 20 yrs of age who underwent (adeno)tonsil-
with abnormal cephalometric measurements. There have been           lectomy were included in the analysis (table e15). Common to
improvements in either sleepiness scales or daytime energy          most reports is that the indication for surgery was based on
levels in six reports, and a reduction in therapeutic CPAP          evidence of upper airway obstruction, either by means of
pressure required to alleviate OSA in two studies.                  clinical signs or symptoms and/or poly(somno)graphically
                                                                    diagnosed sleep disordered breathing. Most studies investi-
Conclusions and recommendations                                     gated the effects of tonsillectomy as a combined procedure
Nasal surgery as a single intervention is not recommended for       with adenoidectomy. The study population was very hetero-
treatment of OSAS (C). Nasal surgery is recommended for             geneous, including children who underwent tonsillectomy
reducing high therapeutic CPAP pressure due to nasal                because of snoring, suspected OSA, poly(somno)graphically
obstruction (C).                                                    verified sleep apnoea (using an apnoea index (AI) .1 or AHI
                                                                    .5 h-1 as a diagnostic cut-off), recurrent tonsillitis, and/or
Tonsillectomy and tonsillotomy                                      symptoms of upper airway obstruction without further
Rationale                                                           explanation. Follow-up studies were performed between a
The main upper airway anatomical alterations correlating            few days postoperatively and up to 12 months after surgery.
with OSA include an enlarged tongue, soft thick palate, web
                                                                    All studies showed significant postoperative improvements in
posteriorised in relation to the oropharynx, long and thick
                                                                    respiratory parameters.
uvula, and/or hypertrophic tonsils. Of note, those studies
attempting to correlate the presence of anatomical alterations      Furthermore, there is some evidence of improved sleep
with disease severity found the highest correlations for            architecture and improved quality of life scores, OSA symptom
tonsillar hypertrophy [184, 185]. While substantial bilateral       scores, and/or child behavioural scores. The literature also
tonsillar hypertrophy in adults is rather rare, adenotonsillar      provides evidence for beneficial treatment effects beyond the
hypertrophy is the most common aetiology of OSA in                  reported outcomes on sleep parameters and quality of life
children. The aim of this literature search was to assess the       scores, such as rapid increase in growth rate [188], improvement
efficacy of surgical tonsillectomy on sleep apnoea severity,        in insulin like growth factor-I levels [189], and improvements in
sleep quality, and symptoms in adults with OSA and tonsillar        systemic inflammation, lipid profiles and endothelial function
hypertrophy.                                                        [190]. Notably, most of the studies that investigated children
                                                                    with moderate to severe OSA observed persistent sleep
Search criteria                                                     disordered breathing in a clinically relevant proportion of
Databases individually searched: PubMed and Medline.                children. Complete resolution of OSA was reported to be as low
Keyword combinations: tonsillectomy and obstructive sleep           as 25% [191]. This raises important issues regarding the efficacy
apnoea, tonsillotomy and obstructive sleep apnoea, tonsils and      of adenotonsillectomy as the only intervention for OSA in
sleep, tonsillar hypertrophy and sleep apnoea, adenotonsil-         children. Accordingly, repeated sleep testing has been recom-
lectomy and sleep apnoea. Studies with tonsillectomy by             mended, particularly in those with persisting symptoms of
means of radiofrequency ablation, studies with tonsillectomy        upper airway obstruction (such as snoring) and/or in those with
as part of UPPP or MLS, and reports on surgical outcomes of         severely abnormal preoperative polysomnography results [192].
the upper airways without explicit information on sleep results
in relation to tonsillectomy were excluded.                         Conclusions and recommendations
                                                                    Tonsillectomy as a single intervention is recommended for
Overview of the evidence in adults                                  treatment of adult OSA in the presence of tonsillar hyper-
All reports have been published either as case series or            trophy (C). Adenotonsillectomy is recommended for treatment
retrospective analyses (table e14). Common to most of the           of childhood OSA in the presence of adenotonsillar hyper-
reports is the lack of quality of life measures, the absence of a   trophy (C).
control group, and the lack of reporting surgical complication
rates. More recent studies, however, reported consistent and        Radiofrequency surgery of the tonsils
significant improvements in the AHI after tonsillectomy.            Rationale
Despite significant improvements in respiratory parameters,         New techniques of tonsillectomy or tonsil volume reduction
there was evidence of residual sleep disordered breathing in        (tonsillotomy) are developed in order to reduce postoperative
most reports. More recent trials by MARTINHO et al. [186] and       pain and bleeding rates. Temperature-controlled radiofre-
NAKATA et al. [187] investigated patients with OSA who where        quency tonsil reduction is performed by introducing a probe
either intolerant to a CPAP trial or required high CPAP             into the tonsil and then heating to temperatures ranging from
pressures to treat upper airway obstruction due to tonsillar        40uC to 70uC. A plasma field consisting of highly ionised
hypertrophy. Based on these reports tonsillectomy play a role       particles is formed at the probe’s surface that breaks down the
similar to nasal surgery in increasing the use of CPAP in           molecular bonds of local tissue, with a reduction in heat
patients with tonsillar hypertrophy, or when CPAP therapy is
not possible as the first choice of therapy.
                                                                    dissipation to surrounding structures. The key innovation of
                                                                    radiofrequency tonsil reduction is the concept of subtotal          c
EUROPEAN RESPIRATORY JOURNAL                                        VOLUME 37 NUMBER 5                                          1009
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